Tumor Models

Members

Judith Favier, PhD
Team 13 - INSERM U970 - PARCC
56 rue Leblanc
75737 PARIS CEDEX 15
France
T: +33 1 53 98 80 41
F: +33 1 53 98 79 52
judith.favier@inserm.fr

Arthur S. Tischler, MD
Department of Pathology
Tufts University School of Medicine
Tufts Medical Center
800 Washington Street, Box 802
Boston, MA 02111
T: (617) 636-1038
F: (617) 636-8302
atischler@tuftsmedicalcenter.org

Karel Pacak, MD, PhD, DSc
Senior Investigator
Chief, Section on Medical Neuroendocrinology Professor of Medicine
Eunice Kennedy Shriver NICHD, NIH
Building 10, CRC, Room 1E-3140
10 Center Drive MSC-1109
Bethesda, Maryland 20892-1109 USA
T: (301) 402-4594
F: (301) 402-4712
karel@mail.nih.gov

Background

Pheochromocytomas and paragangliomas are neuroendocrine tumors that arise, respectively, in the adrenal gland or at various sites in the abdomen, pelvis, head and neck, or chest. At least 15% of these tumors are malignant and can spread to lymph nodes, the skeleton, lungs, and liver. At least 30% are hereditary, with more than 12 susceptibility genes identified to date. Currently there are only minimally effective treatments for patients after metastases occur, and there is no way to prevent the development of tumors in patients with hereditary disease. Animal models and cell lines are needed for basic research on the biology of pheochromocytomas and paragangliomas and for preclinical testing of new treatment strategies.

Our goals

  1. To provide researchers with information on existing models of pheochromocytoma and paraganglioma.
  2. To encourage collaboration that will promote optimal use of existing models and will lead to the development of new ones.

Current status

Mouse Models Related to Pheochromocytoma
Gene Mutation Tumoral phenotype Reference
NF1 NF1+/- Pheo (10-20%,15-28 mo.)
Celllines (‘MPC ‘)
Jacks, Nature Genet 1994
Powers et al,CellTissueRes 2000
RET Met918Thr (het)
Met918Thr (homo)
Chromaffincell hyperplasia (16%)
Chromaffincell hyperplasia (33%)
Pheo (100%, 6-10 months)
Smith-Hicks, EMBO J 2000
VHL VHL-/-
VHL+/-
VHLlox/-, ß-actin-CRE
VHL+/lox, albumin-Cre
Embryoniclethal (E7)
Hepatichemangiomas No Pheo
Hepatichemangiomas
Gnarra, PNAS 1997
Ma, Cancer Res 2003
Haase, PNAS 2001
SDHD SDHD-/-
SDHD+/-
Embryoniclethal (E7)
Carotid body hyperplasia, No Pheo
Piruat, Mol CellBiol 2004
SDHB SDHB-/-
SDHB+/-
SDHBlox
No Pheo Maher et al, 2011
Favier, unpublished
ErbB2 PB-ErbB2 (prostate) Adrenalhypertrophy (5%),
Pheo, (5% of males, 15 mo.)
Lai, Cell Cycle 2007
PTEN Ink4a Arf+/+ ; Pten+/-
Ink4a Arf+/- ; Pten+/-
Ink4a Arf-/- ; Pten+/-
Pheo (23%, 7 months)
Pheo (60% 7.5 months)
Pheo (60% 6 months)
You, PNAS 2002
PTEN PSA-Cre;Pten-loxP/loxP(prostate) Pheo (30%, 7-9 months)
Pheo (88% 10–14 months)
Pheo (100%, 15–16 months)
Korpershoek, J Pathol 2009
c-mos Transgenic BilateralPheo (58%, 8 months) Schultz, Cancer Res 1992

Current Opportunities for Collaboration

Contact: Dr. Jean-Pierre Bayley
Department of Human Genetics
Center for Human and Clinical Genetics
Leiden University Medical Center

Building 2, Postzone: S-04
Room R4-024
P.O. Box 9600
2300 RC Leiden
The Netherlands

Email: j.p.l.bayley@lumc.nl
Tel: +31 71 526 9512
Fax: +31 71 526 8285
Tel Secretariat: +31 71 526 9400

References

  1. Tischler AS, Powers JF, Alroy J, Animal models of pheochromocytoma. Histol Histopathol, 19, 883-95, 2004.
  2. Miller AD, Masek-Hammerman K, Dalecki K, Mansfield KG, Westmoreland SV, Histologic and immunohistochemical characterization of pheochromocytoma in 6 cotton-top tamarins (Saguinus oedipus). Vet Pathol, 46, 1221-9, 2009.
  3. Molatore S, Liyanarachchi S, Irmler M, Perren A, Mannelli M, Ercolino T, Beuschlein F, Jarzab B, Wloch J, Ziaja J, Zoubaa S, Neff F, Beckers J, Hofler H, Atkinson MJ, Pellegata NS, Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma. Proc Natl Acad Sci U S A, 107, 18493-8, 2010.
  4. Gaertner FC, Wiedemann T, Yousefi BH, Lee M, Repokis I, Higuchi T, Nekolla SG, Yu M, Robinson S, Schwaiger M, Pellegata NS, Preclinical Evaluation of 18F-LMI1195 for In Vivo Imaging of Pheochromocytoma in the MENX Tumor Model. J Nucl Med, 54, 2111-7, 2013.
  5. Lee M, Waser B, Reubi JC, Pellegata NS, Secretin receptor promotes the proliferation of endocrine tumor cells via the PI3K/AKT pathway. Mol Endocrinol, 26, 1394-405, 2012.
  6. Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA, Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet, 7, 353-61., 1994.
  7. Maher LJI, Smith EH, Rueter EM, Becker NA, Bida JP, Nelson-Holte M, Palomo JIP, Garci´a-Flores P, Lo´pez-Barneo J, van Deursen J. Mouse Models of Human Familial Paraganglioma. In: Martin JF, ed. Pheochromocytoma - A New View of the Old Problem: InTech, 2011. http://www.intechopen.com/books/pheochromocytoma-a-new-view-of-the-old-problem/mouse-models-of-human-familial-paraganglioma
  8. Powers JF, Evinger MJ, Tsokas P, Bedri S, Alroy J, Shahsavari M, Tischler AS, Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice. Cell Tissue Res, 302, 309-20, 2000.
  9. Ghayee HK, Bhagwandin VJ, Stastny V, Click A, Ding LH, Mizrachi D, Zou YS, Chari R, Lam WL, Bachoo RM, Smith AL, Story MD, Sidhu S, Robinson BG, Nwariaku FE, Gazdar AF, Auchus RJ, Shay JW, Progenitor cell line (hPheo1) derived from a human pheochromocytoma tumor. PLoS One, 8, e65624, 2013.
  10. Tischler AS, Ruzicka LA, Riseberg JC, Immunocytochemical analysis of chromaffin cell proliferation in vitro. J Histochem Cytochem, 40, 1043-5, 1992.
  11. Greene LA, Tischler AS, Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A, 73, 2424-8, 1976.
  12. Martiniova L, Lai EW, Elkahloun AG, Abu-Asab M, Wickremasinghe A, Solis DC, Perera SM, Huynh TT, Lubensky IA, Tischler AS, Kvetnansky R, Alesci S, Morris JC, Pacak K, Characterization of an animal model of aggressive metastatic pheochromocytoma linked to a specific gene signature. Clin Exp Metastasis, 26, 239-50, 2009.
  13. Hopewell R, Ziff EB, The nerve growth factor-responsive PC12 cell line does not express the Myc dimerization partner Max. Mol Cell Biol, 15, 3470-8, 1995.